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Trial record 31 of 751 for:    Anti-Infective Agents AND Antibiotics, Antitubercular AND culture

7 Days Versus 14 Days of Antibiotics for Neonatal Sepsis

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ClinicalTrials.gov Identifier: NCT03280147
Recruitment Status : Not yet recruiting
First Posted : September 12, 2017
Last Update Posted : December 5, 2018
Sponsor:
Collaborators:
Postgraduate Institute of Medical Education and Research, Chandigarh
Chacha Nehru Bal Chikitsalaya, New Delhi
Pandit Bhagwat Dayal Sharma, PGIMS, Rohtak
Institute of Child Health, Chennai
St Johns Medical College Hospital, Bangalore, India
Lady Hardinge Medical College
Information provided by (Responsible Party):
Sourabh Dutta, Postgraduate Institute of Medical Education and Research

Brief Summary:
The optimum duration of intravenous antibiotic therapy for culture-proven neonatal bacterial sepsis is not known. Current practices, ranging from 7 days to 14 days of antibiotics, are not evidence-based. This is a randomized, active -controlled, multi-centric, non-inferiority trial to compare the efficacy of a 7-day course of intravenous antibiotics versus a 14-day course among neonates weighing > 1500 g at birth with culture-proven bacterial sepsis that is uncomplicated by meningitis, bone or joint infections deep-seated abscesses. The primary outcome measure is a definite or probable relapse within 21 days after stoppage of antibiotics.

Condition or disease Intervention/treatment Phase
Infant, Newborn Neonatal SEPSIS Anti-bacterial Agents Recurrence Drug: 7-day course of antibiotics Drug: 14-day course of antibiotics Phase 3

Detailed Description:
The optimum duration of intravenous antibiotic therapy for uncomplicated neonatal bacterial septicemia is not known. Pediatricians administer anywhere between 7 to 14 days of antibiotics, but these practices are not evidence based. C reactive protein (CRP) guided antibiotic duration is based on limited data and serial quantitative CRP is both cumbersome and not universally available. If it could be demonstrated that a 7-day course of antibiotics is not inferior to a 14-day course of antibiotics in terms of relapse rates of infection, then a 7 day course of antibiotics could be uniformly adopted, resulting in economic savings, shorter duration of hospitalization, less chances of hospital acquired infections, less chances of antibiotic induced adverse events and less antibiotic resistance. To test this hypothesis, a randomized, active-controlled, multi-centric, non-inferiority trial to compare the efficacy of a 7-day course of intravenous antibiotics with a 14-day course has been planned. Subjects weighing more than 1500 g at birth with suspected sepsis will be enrolled and observed for a 7-day period to see if they meet eligibility criteria for randomization. Subjects will be randomized on the 7th day of antibiotics, if the initial blood culture grows a non-Staphylococcus aureus bacterial organism, if they have no meningitis, osteomyelitis, septic arthritis or deep seated abscess and if the sepsis goes into clinical remission by the 5th day and remains in remission up to the 7th day of sensitive antibiotics. Subjects in the 14-day group will receive 7 more days of antibiotics after randomization, whereas those in the 7-day group will receive no further antibiotics after randomization. Subjects will be followed up for a 35-day period after randomization. The key outcome will be treatment failure as measured by "definite or probable relapse" within a 21-day period after completion of antibiotic therapy. Secondary outcomes will include definite relapse within 21 and 28 days after antibiotic completion and within 28 and 35 days after randomization; and probable relapse at similar time points. Other secondary outcomes will include secondary infections and adverse events. A total sample size of 1000 (500 in each arm) will be required to detect a non-inferiority margin of 5%, assumed event rate of 10%, with 90% power, one-sided alpha error of 5% and loss to follow-up of approximately 10%. Data safety monitoring board will monitor serious adverse events in the trial and will perform one mid-term analysis when about 50% of the expected primary outcomes have occurred or when 50% of the subjects have completed their follow-up as per protocol, whichever is earlier. At the time of interim analysis, the DSMB will revisit the sample size of the study. O'Brien Fleming's stopping criteria will be used for the primary outcome while Pocock's stopping rule will be used for the serious adverse events.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, outcome-assessor blinded, active-controlled, multi-centric, non-inferiority trial
Masking: Single (Outcomes Assessor)
Masking Description: Outcome assessor will be provided objective clinical information related to episodes of all illnesses during follow-up with all patient identifiers removed and the record identified only by a unique code number. All imaging films and investigation reports provided to the outcome assessor will be similarly bereft of patient identifiers and coded by a unique code number. The outcome assessor will not be involved in the rest of the study. The outcome assessor will adjudicate whether the given episode of illness is a relapse.
Primary Purpose: Treatment
Official Title: Comparison of the Efficacy of a 7-day Versus 14-day Course of Intravenous Antibiotics in the Treatment of Uncomplicated Neonatal Bacterial Sepsis: a Randomized Controlled Non-inferiority Trial
Estimated Study Start Date : January 1, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Sepsis

Arm Intervention/treatment
Experimental: 7-day course of antibiotics
Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 7-day group will not receive any further antibiotics.
Drug: 7-day course of antibiotics
Subjects in the "7-day course of antibiotics" arm of the study will receive no further antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.

Active Comparator: 14-day course of antibiotics
Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 14-day group will receive 7 more days of the same antibiotics, to make it a total of 14 days.
Drug: 14-day course of antibiotics
Subjects in the "14-day course of antibiotics" arm of the study will receive 7 more days of antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.




Primary Outcome Measures :
  1. Definite or probable relapse within 21 days post-antibiotic completion as per protocol [ Time Frame: From 0-21 days after the end of the planned antibiotic therapy ]
    Among participants who adhered to study protocol- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  2. Definite or probable relapse within 21 days post-antibiotic completion as per intention to treat [ Time Frame: From 0-21 days after the end of the planned antibiotic therapy ]
    Among all randomized patients- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.


Secondary Outcome Measures :
  1. Definite relapse within 21 days post-antibiotic completion, as per protocol [ Time Frame: From 0-21 days after the end of the planned antibiotic therapy ]
    Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  2. Definite relapse within 21 days post-antibiotic completion, as per intention-to-treat [ Time Frame: From 0-21 days after the end of the planned antibiotic therapy ]
    Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  3. Definite relapse within 28 days post-antibiotic completion, as per protocol [ Time Frame: From 0-28 days after the end of the planned antibiotic therapy ]
    Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  4. Definite relapse within 28 days post-antibiotic completion, as per intention-to-treat [ Time Frame: From 0-28 days after the end of the planned antibiotic therapy ]
    Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  5. Definite relapse within 28 days post-randomization, as per protocol [ Time Frame: From 0-28 days after randomization ]
    Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  6. Definite relapse within 28 days post-randomization, as per Intention-to-treat [ Time Frame: From 0-28 days after randomization ]
    Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  7. Definite relapse within 35 days post-randomization, as per protocol [ Time Frame: From 0-35 days after randomization ]
    Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  8. Definite relapse within 35 days post-randomization, as per intention to treat [ Time Frame: From 0-35 days after randomization ]
    Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode

  9. Probable relapse within 21 days post-antibiotic completion, as per protocol [ Time Frame: From 0-21 days after the end of the planned antibiotic therapy ]
    Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  10. Probable relapse within 21 days post-antibiotic completion, as per intention-to-treat [ Time Frame: From 0-21 days after the end of the planned antibiotic therapy ]
    Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  11. Probable relapse within 28 days post-antibiotic completion, as per protocol [ Time Frame: From 0-28 days after the end of the planned antibiotic therapy ]
    Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  12. Probable relapse within 28 days post-antibiotic completion, as per intention-to-treat [ Time Frame: From 0-28 days after the end of the planned antibiotic therapy ]
    Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  13. Probable relapse within 28 days post-randomization, as per protocol [ Time Frame: From 0-28 days after randomization ]
    Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  14. Probable relapse within 28 days post-randomization, as per intention-to-treat [ Time Frame: From 0-28 days after randomization ]
    Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  15. Probable relapse within 35 days post-randomization, as per protocol [ Time Frame: From 0-35 days after randomization ]
    Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  16. Probable relapse within 35 days post-randomization, as per intention-to-treat [ Time Frame: From 0-35 days after randomization ]
    Among all randomised patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  17. Definite relapse or probable relapse within 28 days post-randomization, as per protocol [ Time Frame: From 0-28 days after randomization ]
    Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  18. Definite relapse or probable relapse within 28 days post-randomization, as per Intention-to-treat [ Time Frame: From 0-28 days after randomization ]
    Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  19. Definite relapse or probable relapse within 35 days post-randomization, as per protocol [ Time Frame: From 0-35 days after randomization ]
    Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  20. Definite relapse or probable relapse within 35 days post-randomization, as per intention-to-treat [ Time Frame: From 0-35 days after randomization ]
    Among all randomised patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  21. Secondary sepsis [ Time Frame: From 0-35 days after randomization ]
    Sepsis due to bacterial organisms other than the original etiologic bacteria or with a different antibiogram or with a fungal organism

  22. Adverse events [ Time Frame: From 0-35 days after randomization ]
    Adverse events as per a list of adverse events, graded as per severity, and defined a priori



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion criteria for the initial observation part of study preceding randomization

  1. Neonates aged 0-28 days, either inborn or outborn, who are currently admitted in the Neonatal Unit of the centre.
  2. Whose birth weight is greater than 1500 grams (it should be reliably ascertained from records of a hospital)
  3. Whose residence is within approximately 15 kms from the center, so that the infant can be brought back to the center for follow-up
  4. Who have suspected septicemia for which a conventional or BACTEC/BACTALERT blood culture is sent and for which the treating physician decides to start antibiotics

Inclusion criteria for Randomization applicable after 7 days of therapy of above patients with sensitive antibiotics:

  1. Positive blood culture other than Staphylococcus aureus
  2. No signs and symptoms of sepsis from end of day 5 through end of day 7 of starting sensitive antibiotics

Exclusion Criteria:

Exclusion criteria for the initial observation part of study preceding randomization:

  1. Suspected meniingitis (meningitis will be defined as one or more of CSF cell count more than or equal to 25 per microliter with > 60% neutrophils; glucose 180 mg/dL in preterm or positive gram stain report)
  2. Septic arthritis, osteomyelitis or deep-seated abscess as clinically judged by the treating team
  3. Life threatening congenital malformations as judged by the principal investigator of the centre

Exclusion criteria for randomization applicable after 7 days of therapy of above patients with sensitive antibiotics:

  1. Sterile blood culture
  2. Suspected contaminants in blood culture.
  3. Growth of Staphylococcus aureus in blood culture
  4. Growth of fungal organism in blood culture
  5. Diagnosis of meningitis, septic arthritis, osteomyelitis, abscess
  6. Has not gone into remission on day 5 or have recurrence of symptoms from day 5 through day 7
  7. If the empiric antibiotic is resistant but neonate has shown improvement of signs and symptoms of sepsis and there is ambiguity regarding in vivo sensitivity of antibiotic use

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03280147


Contacts
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Contact: Reeta Rasaily +91-9818635958 reeta.rasaily@gmail.com

Locations
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India
Pandit BD Sharma Postgraduate Institute of Medical Sciences Not yet recruiting
Rohtak, Haryana, India, 124001
Contact: Geeta Gathwala    +91-9896489650    geetagathwala@gmail.com   
St Johns Medical College Hospital Not yet recruiting
Bangalore, Karnataka, India, 560034
Contact: Suman Rao    +91-9019569652    raosumanv@rediffmail.com   
Institute of Child Health Not yet recruiting
Chennai, Tamil Nadu, India, 600008
Contact: Sundaram Mangalabharti    9840786836    drmangalabharti@gmail.com   
Postgraduate Institute of Medical Education and Research Not yet recruiting
Chandigarh, India, 160023
Contact: Sourabh Dutta, MD, PhD    +91-8283831967    sourabhdutta1@gmail.com   
Kalawati Saran Childrens Hospital and Lady Hardinge Medical College Not yet recruiting
New Delhi, India, 110001
Contact: Sushma Nangia    +91-9810838181    drsnangia@gmail.com   
Chacha Nehru Bal Chikitsalaya Not yet recruiting
New Delhi, India, 110031
Contact: Mamta Jajoo    +91-9643308217    mamtajajoo123@gmail.com   
Sponsors and Collaborators
Indian Council of Medical Research
Postgraduate Institute of Medical Education and Research, Chandigarh
Chacha Nehru Bal Chikitsalaya, New Delhi
Pandit Bhagwat Dayal Sharma, PGIMS, Rohtak
Institute of Child Health, Chennai
St Johns Medical College Hospital, Bangalore, India
Lady Hardinge Medical College
Investigators
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Principal Investigator: Sourabh Dutta Postgraduate Institute of Medical Education and Research
  Study Documents (Full-Text)

Documents provided by Sourabh Dutta, Postgraduate Institute of Medical Education and Research:
Study Protocol  [PDF] October 15, 2018
Statistical Analysis Plan  [PDF] October 15, 2018


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Responsible Party: Sourabh Dutta, Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT03280147     History of Changes
Other Study ID Numbers: 5/7/329/2009-RHN
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Sourabh Dutta, Postgraduate Institute of Medical Education and Research:
Neonate
Sepsis
Antibiotics
Duration
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Sepsis
Toxemia
Neonatal Sepsis
Recurrence
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Disease Attributes
Infant, Newborn, Diseases